A novel antifungal antibiotic FR-900848 was recently discovered which possesses an unprecedented five cyclopropane units on a single fatty acid backbone. Four of these cyclopropane units are contiguous thereby creating a functionally we have called polycyclopropanes. This unusual structure prompts many questions about the interaction of configuration, conformation, and antifungal activity. The relationship of these can be studied through the effective synthesis of polycyclopropanes and polycyclopropanated fatty acids. The primary goal of this proposed study is the development of synthetic methods for the preparation of polycyclopropanated fatty acids. It is imperative that these syntheses be stereoselective. Many potential approaches to these polycyclopropanes are outlined including interactive approaches using Simmons-Smith type reagents, Rhodium carbenoids, and sulfur ylides. Two-directional application of these approaches will lead to the rapid increase in complexity. A classical synthetic approach starting from mannitol is proposed to yield an enantioselective synthesis of a specific tricyclopropane. The assignment of configurational isomers for these new products will rely upon a combination of methods including NMR and synthetic correlation. It is proposed that the antifungal activity of FR-900848 is due to interaction with the fungal cell membrane. The polycyclopropane dimers and trimmers will be incorporated into fatty acids and their interaction with lipid bilayer studied by FT-IR. The phase transition temperature of the lipids and the changes in gauche conformer interaction of the lipid chains will be monitored. The relationship of polycyclopropane structure and conformation to membrane interaction may shed light on the requirements for antifungal activity. Molecular modeling has demonstrated that one of the regular polycyclopropanes may exist as a helical structure. The stereoselective synthesis of this regular isomer is set as a target. Methods for determination of the conformation of the polycyclopropanated species are proposed. The potential uses of a non-peptide a-helix mimic can range from artificial enzymes to molecular scaffolding to DNA recognition.